N-Methylimidazole

[616-47-7]  · C4H6N2  · N-Methylimidazole  · (MW 82.12)

(phosphorylation; acylation)

Physical Data: bp 195-197 °C; d 1.031 g cm-3.

Solubility: usually used in THF, Et2O.

Form Supplied in: redistilled liquid (99+%); packed under nitrogen.

Analysis of Reagent Purity: the reagent may be analyzed using standard techniques.

Purification: dried with sodium metal and then distilled.

Handling, Storage, and Precautions: store at 0 °C under dry argon. The compound is harmful in contact with skin and if swallowed, and causes burns.

Introduction.

N-Methylimidazole is used for phosphorylation and acylation. It can be lithiated at the 2-position by treating with n-Butyllithium at -78 °C in THF or diethyl ether. The Grignard reagent can also be prepared by exchange with Ethylmagnesium Bromide at the 2-position.1

Phosphorylation.

Alcohols may be phosphorylated in good yield by the reaction of phosphorous acid, mercury(II) chloride and N-methylimidazole (eq 1). An intermediate salt (1) is formed. This method has been used to prepare nucleoside 5-phosphates in yields of 60-70%.2 Similarly, amines may be phosphorylated by reaction with Phosphorus Oxychloride and N-methylimidazole (eq 2).3

Acylation.

N-Methylimidazole reacts with acid chlorides and chloroformates to give N-acylimidazolium salts. These can then be used as effective acylating agents, for example of amines, in aqueous solution (eq 3).4

N-Methylimidazole has been used as an effective catalyst of acylation by Acetic Anhydride. It has a catalytic activity about 4 × 102 greater than pyridine (eq 4).5

Reactions of 2-Lithio-1-methylimidazole.

2-Lithio-1-methylimidazole reacts with ketones at -78 °C in 65-96% yield to give 2-(1-hydroxyalkyl)-1-methylimidazoles. These can be dehydrated with hot acetic anhydride to give 2-vinyl-1-methylimidazoles in 73-85% yield (eq 5).6

2-Lithio-1-methylimidazole reacts with alkyl or aryl nitriles to give 2-acyl-1-methylimidazoles (acid anhydrides, acid chlorides and amides give poor, nonreproducible yields of the ketones). These then yield 1-methylimidazolethylenes via a Wittig reaction. Vinylimidazoles are reported to be potentially useful as monomers in the synthesis of heterocyclic polymers (eq 6).7

2-Imidazolylsilanes may be synthesized by reacting Chlorotrimethylsilane with 2-lithio-1-methylimidazole and subsequent transsilylation (eq 7).8


1. Somin, I. N.; Kizimova, G. V. ZOB 1969, 39, 1854.
2. Takaku, H.; Shimada, Y.; Oka, H. CPB 1973, 21, 1844.
3. Jampel, E. G.; Wakselman, M.; Vilkas, M. BSF 1971, 1308.
4. Jampel, E. G.; Bram, G.; Vilkas, M. BSF 1973, 1021.
5. Connors, K. A.; Pandit, N. K. Anal. Chem. 1978, 50, 1542.
6. Ohta, S.; Matsukawa, M.; Ohashi, N.; Nagayama, K. S 1990, 78.
7. Abarca-Gonzalez, J.; Sepulveada-Arques, J.; Zaballos-Garcia, E. SC 1990, 20, 321.
8. Jutzi, P.; Jakriss, W. CB 1969, 106, 2815.

Craig Tindall

University of Bristol, UK



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